This proposal requests funds to purchase a Tecnai Spirit 120-kV electron microscope for high-contrast and high-throughput routine imaging. The new instrument will be housed in the multi-disciplinary Electron Microscopy (EM) Facility. This core facility currently houses an intermediate-voltage 300-kV FEI Tecnai F30 transmission electron microscope, which is well suited to physical science applications and to electron tomography. However, for the routine needs of biomedical researchers in the Biological Sciences Division, the F30 is far from optimal for the following reasons. (1) Although the high accelerating voltage makes the F30 suitable for high-resolution structural analysis and for analyzing thick sections, the contrast is less than ideal for traditional thin-section EM of biological material. (2) The F30 operates with a high vacuum, and requires 3-5 minutes of down time between each change of samples. When multiple samples are being examined, the cumulative delay becomes substantial. (3) The F30 is a very complex and delicate instrument, and authorization to use the F30 requires an extensive 8- to 10-hr training session. As a result, many investigators either rely on assistance from facility experts during regular business hours, or forgo EM analysis entirely. (4) The F30 is occupied for long periods by physical scientists, and by biologists who are collecting tomographic data sets. Therefore, access for routine imaging is often difficult. Acquisition of the Tecnai Spirit will overcome these limitations. This instrument is ideally suited to high-contrast imaging of biological thin sections. Sample exchange can be performed rapidly, enabling high-throughput analyses. The Tecnai Spirit is relatively simple and robust, and researchers can be readily trained to operate this instrument themselves. Availability of a high-quality microscope for routine EM of biological samples will particularly benefit NIH-funded research programs. The Biological Sciences Division at University of Chicago employs many investigators who use EM. Research topics range from basic cell biology and microbiology to studies of diabetes and asthma. The Division invests major resources in establishing and maintaining core facilities that support cutting-edge science. Acquisition of the Tecnai Spirit will help to ensure that the Electron Microscopy Facility meets this standard. This instrument will be managed by an accomplished and knowledgeable staff, and will be accessible to a broad range of researchers.